Embryonic stem cells (ESCs) are derived from the inner cell mass (ICM) of the blastocyst. ESCs are able to differentiate into three germ layers and potentially all cells from the adult body.
This pluripotent characteristic makes them desirable in the field of regenerative medicine and provides an invaluable tool for dissecting early embryonic development. Even though ESCs share this property with the pluripotent epiblast cells of the inner cell mass, differences have been observed.
While it would be of great benefit to have a human embryonic stem cell (hESC) state that closely resembles in vivo development, it is not clear how far the in vitro culture conditions of hESCs are limited in imitating the environment of the blastocyst where pluripotency exists only transiently.
In mouse, it has been reported that multiple cell types fulfill the requirements of pluripotency and that these distinct cells match different embryonic developmental stages.
Factor mediated isolation of different pluripotent states has also been successfully applied on human cells, showing the in principle feasibility to interconvert between multiple pluripotent cell types.
In order to obtain hESCs which more closely resemble the native pluripotent epiblast, a transgene free method would be advantageous.
Accordingly, it is an aim of the present invention to provide and maintain a pluripotent stem cell state that ameliorates the disadvantages of the prior art and differentiates more efficiently.